Inflammatory neurological diseases are a class of conditions in which a subject's immune system targets or attacks components of the neurological system. These diseases can result from the immune system attacking, for example, neurons, Schwann cells or other cells of the nervous system myelin or neurotransmitters. In some cases, the inflammatory neurological disease may be a complication or a component of an existing disease, e.g., Exemplary inflammatory neurological diseases include multiple sclerosis, systemic lupus erythematosus (SLE), Guillain-Barre syndrome, Lambert-Eaton myasthenic syndrome, myasthenia gravis, transverse myelitis, leukodystrophy or progressive multifocal leukoencephalopathy.
MS is one of the more common inflammatory neurological diseases. It is an inflammatory and demyelinating degenerative disease of the human central nervous system (CNS). It is a worldwide disease that affects approximately 300,000 people in the United States alone. The majority of people affected by MS (about 70%-80% of cases) show onset between 20 and 40 years of age. MS is a heterogeneous disorder based on clinical course, magnetic resonance imaging (MRI) scan assessment, and pathology analysis of biopsy and autopsy material. The disease manifests itself in a large number of possible combinations of deficits, including spinal cord, brainstem, cranial nerve, cerebellar, cerebral, and cognitive syndromes. Progressive disability is the fate of most patients with MS. About half of MS patients require a cane to walk within 15 years of disease onset.
MS presents in most cases (about 80%) with clinical relapses characterized by fully or partially-reversible focal neurological deficits. This form of MS is known as relapsing-remitting MS (RRMS), and is dominated by inflammation and oedema. Active inflammation of the CNS is visualized as gadolinium enhancing white matter lesions on MRI. After a median of about 39 years, about half of RRMS cases gradually accumulate irreversible neurologic deficits in the absence of clinical relapses or new white matter lesions as detected by MRI. This stage of disease is known as secondary progressive MS (SPMS) or chronic disease. The 20% of patients who do not present with RRMS present with progressive clinical deterioration from the onset of disease, which is known as primary progressive MS (PPMS), which is another form of chronic disease.
Currently, acute MS relapses are usually treated with high-dose, short-term intravenous corticosteroids. This treatment shortens relapse duration but does not improve the degree of recovery or the long-term course of disease. There are currently several approved disease-modifying therapies approved in USA, which are intended to lower the clinical relapse rate, extend the time to next relapse and/or reduce the accumulation of new lesions on MRI. However, these therapies are only moderately effective for treating MS, particularly during the relapsing-remitting phase. These treatments also merely retard the progression of disease and do not result in remyelination.
SLE is an inflammatory disease affecting various organ systems in the body. Subjects suffering from SLE can develop various neurological disorders such as headaches, personality changes, organic brain syndrome, peripheral neuropathies, sensory neuropathy, psychological problems including paranoia, mania, and schizophrenia, seizures, transverse myelitis, and paralysis and stroke. Some of these changes can be brought on by antiphospholipid antibodies (e.g., anti-cardiolipin antibodies), which can bind to cells of the central nervous system and disrupt function and/or thrombosis.
Common pharmacological treatments for lupus include the use of corticosteroids or immunosuppressive drugs, both of which have undesirable side effects and merely treat the symptoms as they occur.
Other inflammatory neurological diseases are treated using, for example, immunosuppressive drugs, corticosteroids, plasmapheresis or intravenous immunoglobulin, each of which carry a risk of infection or other adverse side effect.
It will therefore be apparent to those skilled in the art that there is a need in the art for new therapies useful for treating inflammatory neurological diseases.